Biology subjects

Tokuda, I. T.

Publications and source records attributed to Tokuda, I. T..

6 recordsLinked to original sources

bioRxiv2025

Data-driven mathematical modelling explains altered timing of EARLY FLOWERING 3 in the wheat circadian oscillator

Circadian rhythms, daily oscillations with a free-running period of approximately 24 hours, have evolved in organisms across the kingdoms of life, enabling organisms to anticipate and adapt to environmental cycles. Circadian timing in plants is governed by an oscillator gene network of transcriptional regulators that exists in each cell. Wheat provides an opportunity to investigate the mechanisms of the plant circadian oscillator in an important agricultural species. We recently found that a single oscillator component EARLY FLOWERING 3 is expressed at a different time in wheat compared to the model plant Arabidopsis. This was unexpected since there is remarkable conservation of timing of activity of the different oscillator components within a kingdom, for example, even when animals switch from nocturnal to diurnal activity. We have examined how the change in timing of ELF3 transcription between Arabidopsis and wheat has occurred and its implications for circadian oscillator function. We describe an optimised computational model of the wheat circadian oscillator that is informed by experimental data and the structure of the promoter elements driving oscillator gene expression. Our optimised computational models suggest that the dawn-expression of the key oscillator gene ELF3 in wheat occurs due to repression of the ELF3 promoter by TOC1. Our simulations predict that plant circadian oscillators are robust against changes in ELF3 timing. Our work demonstrates that plant circadian oscillators can have a flexible architecture such that different oscillator structures can originate circadian rhythms.

plant biology↗

bioRxiv2020

A spatial model of the plant circadian clock reveals design principles for coordinated timing under noisy environments

Individual plant cells possess a genetic network, the circadian clock, that times internal processes to the day-night cycle. Mathematical models of the clock network have driven a mechanistic understanding of the clock in plants. However, these models are typically either whole plant models that ignore tissue or cell type specific clock behavior, or phase only models that do not include clock network components explicitly. It is increasingly clear that in order to reveal the design principles of the plant circadian clock, clock network models must address spatial differences. This is because complex spatial behaviours have been observed in tissues and cells in plants, including period and phase differences between cells and spatial waves of gene expression between organs. Here, we implement an up to date clock network model on a spatial template of the plant. In our model, the sensitivity to light inputs varies across the plant, and cells communicate their clock timing locally via the levels of core clock mRNA levels by cell-to-cell coupling. We found that differences in sensitivities to environmental input in the model can explain the experimentally observed differences in clock periods in different organs, and we show using the model that a plausible coupling mechanism can generate the experimentally observed waves in clock gene expression across the plant. We then examined what features of the plant circadian system allow it to keep time under noisy light-dark (LD) cycles. We found that differences in sensitivity to light can allow regional flexibility in phase even under LD cycles, whilst local cell-to-cell coupling minimized variability in clock rhythms in neighboring cells. Thus, local sensitivity to environmental inputs combined with cell-to-cell coupling allows for flexible yet robust circadian timing under noisy environments.

plant biology↗

bioRxiv2019

Conceptual models of entrainment, jet-lag, and seasonality

Understanding entrainment of circadian rhythms is a central goal of chronobiology. Many factors, such as period, amplitude, Zeitgeber strength, and day-length, govern entrainment ranges and the phase of entrainment. Using global optimization, we derive conceptual models with just three free parameters (period, amplitude, relaxation rate) that reproduce known phenotypic features of vertebrate clocks: relatively small phase response curves (PRCs), fast re-entrainment after jet-lag, and seasonal variability to track light onset or offset. Since optimization found multiple sets of model parameters, we can study this model ensemble to gain insight into the underlying design principles. We find that amplitudes control the size of PRCs, that fast relaxation supports short jet-lag, and that specific periods allow reasonable seasonal phase shifts. Arnold onions of representative models visualize strong dependencies of entrainment on periods, relative Zeitgeber strength, and photoperiod.

systems biology↗

bioRxiv2019

Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics

Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this \"presumably transient\" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.

systems biology↗

bioRxiv2019

Electrical coupling controls dimensionality and chaotic firing of inferior olive neurons

One of the main challenges facing online neural learning systems with numerous modifiable parameters (or "degrees-of-freedom") such as the cerebellum, is how to avoid "overfitting". We previously proposed that the cerebellum controls the degree-of-freedoms during learning by gradually modulating the electric coupling strength between inferior olive neurons. Here, we develop a modeling technique to estimate effective coupling strengths between inferior olive neurons from in vivo recordings of Purkinje cell complex spike activity in three different coupling conditions. We show that high coupling strengths induce synchronous firing and decrease the dimensionality of inferior olive firing dynamics. In contrast, intermediate coupling strengths induce chaotic firing and increase the dimensionality of firing dynamics. Our results thus support the hypothesis that effective coupling controls the dimensionality of inferior olive firing, which may allow the olivocerebellar system to learn effectively from a small training sample set despite the low firing frequency of inferior olive neurons.

neuroscience↗

bioRxiv2017

Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression

The Arabidopsis circadian clock orchestrates gene regulation across the day/night cycle. Although a multiple feedback loop circuit has been shown to generate the 24h rhythm, it remains unclear how robust the clock is in individual cells, or how clock timing is coordinated across the plant. Here we examine clock activity at the single cell level across Arabidopsis seedlings over several days. Our data reveal robust single cell oscillations, albeit desynchronised. In particular, we observe two waves of clock activity; one going down, and one up the root. We also find evidence of cell-to-cell coupling of the clock, especially in the root tip. A simple model shows that cell-to-cell coupling and our measured period differences between cells can generate the observed waves. Our results reveal the spatial structure of the plant circadian clock and suggest that unlike the centralised mammalian clock, the clock has multiple points of coordination in Arabidopsis.

systems biology↗